Relatives Claim Surrogate Role for Alzheimerâ€™s Informed Consent

Action Points

Understand that a majority of relatives of people with Alzheimer's disease who are themselves at risk for Alzheimer's would be willing to participate in surrogate-consent based clinical treatment trials themselves, and allow their relatives to be enrolled, particularly when the risks are low to moderate.

Inform interested patients that informed consent laws governing participation in clinical trials by patients or their surrogates (e.g., parents, guardians) vary from state to state.

ANN ARBOR, Mich. - When it comes to clinical trials for Alzheimer's disease, relatives of patients generally believe it is ethically proper for them, as familial surrogates, to assume the responsibility of informed consent, particularly if the study carries only a mild-to-moderate risk. They would also accept this surrogate role for themselves.

Ninety percent of respondents in a survey about the ethics of medical research agreed that relatives can be surrogates in low-risk trials -- such as a study of a new drug -- for those who are not fully capable of giving consent, according to psychiatrist Scott Y.H. Kim, M.D., Ph.D. of the University of Michigan and colleagues here and the University of Rochester.

A smaller but still significant proportion said that it would be okay for someone else to enroll a person with Alzheimer's into studies where the health stakes were higher, such as studies involving gene transfer, lumbar punctures, brain biopsies, and Alzheimer's immunotherapeutic vaccination, the investigators reported in the Nov. 8 issue of Neurology.

"The purpose of this study was to elicit the views of those at heightened risk of Alzheimer's disease regarding how they would balance the need for research in Alzheimer's with the need to protect vulnerable, incapacitated subjects," the authors wrote.

There is currently a hodgepodge of state laws -- and in some states no regulation at all -- regarding when and how it's appropriate for a surrogate to enroll into a clinical trial an adult who is unable to grant informed consent because of dementia or mental illness.

"Right now, Alzheimer's studies being done in one state could be illegal in others, and most states such as Michigan have no clear law on this issue," said Dr. Kim.

The stakeholders in this case were people participating in a study of anti-inflammatory agents for prevention of Alzheimer's. The survey participants were themselves at risk for Alzheimer's. All were older than 70, and all had at least one close blood relative who had been diagnosed with Alzheimer's.

The participants were asked about the acceptability of 10 surrogate-consent based research scenarios involving varying degrees of risk, from simple observation studies to gene-transfer protocols. They were also asked to rate the scenarios from a social policy standpoint, as well as their preferences for participating in such studies themselves, or when they were acting on behalf of another.

In all, 229 of 259 people (88%) who were solicited for participation returned the surveys.

There was strong support for surrogate-based research with relatively low risk, even when there is no potential for direct benefit to the subjects. For research scenarios with significant risks and burdens, although the acceptability rate is lower, a majority still found the policy of surrogate consent acceptable.

The investigators found that more than 90% favored low-risk studies involving observation, blood draws, or randomized drug trials. Slightly more than half (56%) said that brain biopsy should either "definitely" or "probably" be allowed by society, and 54% supported gene-transfer studies.

When asked about the acceptability of a particular type of surrogate-consent based trial from various perspectives, respondents were generally most willing to be guinea pigs themselves, somewhat less in agreement with the notion that such research is for the good of society, and still less willing to subject a loved one to it.

For example, while 69% of respondents said they'd be willing to undergo a lumbar puncture themselves, 65% said it was acceptable from a societal perspective, and 61% said it was acceptable if performed on a relative.

The authors acknowledged that one limitation of their study is that the participants were self-selected by virtue of being enrolled in Alzheimer's prevention study.

"This self-selection is reflected in the fact that almost all our respondents were white, most were financially stable and well educated, and most had completed an advance directive (either a living will or appointing proxy) for healthcare," the investigators said. "Also, because our respondents were already volunteers in research, they may have been more pro-research than the typical elderly person at heightened risk of Alzheimer's."

"The ethics of research involving adults who cannot consent for themselves has been debated for nearly three decades in this country without a clear resolution," Dr. Kim said. "There are no a priori right answers, but a policy should take into account the views of those who will be most affected by it."

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine